Gene therapy provides a possible means to deliver anti-inflammatory biological agents, such as interleukin-10, for long-term treatment of autoimmune arthritis. Adenoviral vector mediated gene therapy allows for high expression of these therapeutic proteins. However, this expression is normally short-lived, in part due to immunogenicity of the viral vector and/or transgenic protein being expressed. Studies outlined in the first two specific aims will determine whether transgene expression can be prolonged utilizing adenoviral vectors engineered to reduce immunogenicity to the adenoviral vector and/or transgenic protein product. The third specific aim functionally tests these vectors in the CIA mouse model system for their effects on autoimmune arthritis. The studies outlined in this proposal will provide valuable data in furthering the development of gene therapy for autoimmune arthritis.